Platelet activation is an early step in many allergic and inflammatory reactions. A key mediator to platelet activation is a glycerol ether lipid containing an acetyl-group. "Platelet-activating factor" (PAF), a natural compound having the structural formula: 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC), as described by Demopoulos et al. in the J. Biol. Chem. 254, 9355-9358 (1979).
PAF is excreted by several types of leukocytes and other cells after immunological and/or certain types of nonimmunological stimulation. The compound activates platelets to aggregate and excrete serotonin, histamine and several granular constituents. In addition, PAF has a wide spectrum of diverse, intravascular, cardiovascular-pulmonary and cutaneous effects, including vasodilation, hypotension, increase in vascular constriction and edema.
Due to the number of effects PAF exerts on the body, some of which are detrimental, such as asthma, it is desirable to have inhibitors of PAF activity and secretion. Unfortunately, to date, there have been no compounds which act in a specific manner to either inhibit secretion or the action of PAF on leukocytes or platelets.
It is therefore an object of the present invention to provide compounds which specifically inhibit PAF activity.
It is another object of the present invention to provide dihydroxy alkyl glycerols with vicinal hydroxyl groups and their acetyl derivatives having biological activity, and methods for their synthesis.